A mechanobiological mathematical model of liver metabolism

Abstract

The liver plays a complex role in metabolism and detoxification, and better tools are needed to understand its function and to develop liver‐targeted therapies. In this study, we establish a mechanobiological model of liver transport and hepatocyte biology to elucidate the metabolism of urea and albumin, the production/detoxification of ammonia, and consumption of oxygen and nutrients. Since hepatocellular shear stress (SS) can influence the enzymatic activities of liver, the effect of SS on the urea and albumin synthesis are empirically modeled through the mechanotransduction mechanisms. The results demonstrate that the rheology and dynamics of the sinusoid flow can significantly affect liver metabolism. We show that perfusate rheology and blood hematocrit can affect urea and albumin production by changing hepatocyte mechanosensitive metabolism. The model can also simulate enzymatic diseases of the liver such as hyperammonemia I, hyperammonemia II, hyperarginemia, citrollinemia, and argininosuccinicaciduria, which disrupt the urea metabolism and ammonia detoxification. The model is also able to predict how aggregate cultures of hepatocytes differ from single cell cultures. We conclude that in vitro perfusable devices for the study of liver metabolism or personalized medicine should be designed with similar morphology and fluid dynamics as patient liver tissue. This robust model can be adapted to any type of hepatocyte culture to determine how hepatocyte viability, functionality, and metabolism are influenced by liver pathologies and environmental conditions.

Preoperative Transient Elastography in Patients with Esophageal Cancer

“…The Child-Pugh score is composed of serum albumin level, serum bilirubin level, prothrombin time, the amount of ascites and the presence of hepatic encephalopathy [ 18 ]. Nevertheless, the three serologic tests could not completely represent the complicated hepatic functions including catabolism, detoxication, anabolism and bile secretion [ 19 , 20 , 21 ]. This might partially answer the inconsistency between the low preoperative Child-Pugh score and the occurrence of postesophagectomy hepatic insufficiency or failure.…”

Mathematical models for biomarker calculation of drug-induced liver injury in humans and experimental models based on gadoxetate enhanced magnetic resonance imaging

“…There are detailed models for use with data from liver perfusion, e.g. for describing uptake kinetics in first passage of blood circulation [27,28]. Such models could in principle be used to improve the 'whole-body model' which was used here, although they describe other functional aspects of the liver.…”

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function

“…However, linking metabolic pathway models to mechanotransduction and mechano-signaling has rarely been established. One such example is a mechanobiological model to study the effect of shear stress on urea and albumin synthesis (Nikmaneshi et al, 2020 ).…”